We shall use somatic cell genetic techniques to analyze the role of Lyt2 (T8), L3T4 (T4) and Ly5 (T200) in the function and differentiation of cells of the T lineage. We have developed methods of producing somatic variants of cloned normal and transformed cells, and we propose to use these techniques to select cell lines of "normal" T cells or T-cell precursors which either lack or express an altered form of a surface marker which normally serves as a differentiation antigen or cell lineage marker. We shall also produce cell lines which egregiously express markers normally present in other cells of the lineage or are derived from other species. We shall clone these cells, grow them in mass culture and study their antigenic structure, genetic organization, biological behavior and functional properties, comparing them with both their parent line and with immunoselected revertants. Specifically, we plan to prepare variants of a cultured prothymocyte line which prematurely express Lyt2 (or OKT8) and L3T4 (or OKT4) and study their subsequent differentiation. We will also prepare variants of helper T cell lines which either lack L3T4, or express either the human equivalent antigen (OKT4) or express the antigen associated with the suppressor phenotype (OKT8).